tbuckley/cabot-search huggingface dataset:
LGG-51. Resection extent and BRAF V600E mutation status determine postoperative growth velocity in pediatric Low-grade glioma: Results from a single-center cohort analysis
Authors: David Gorodezki, Jordana Sosa, Ursula Holzer, Manon Queudeville, Julian Zipfel, Andrea Bevot, Jens Schittenhelm, Thomas Nägele, Martin Ebinger, Martin Schuhmann
Journal: Neuro-Oncology (2022)

Abstract Despite the favourable outcome and excellent long-term overall survival rates, pediatric LGG show vast variety of clinical behavior and limited predictability regarding progress or senescence. We comparatively analyzed the tumor growth velocity (TGV) of PLGG post subtotal resection (STR) to investigate the impact of surgery, histological subtype, tumor location and the most frequent BRAF aberrations (BRAF V600E mutation vs KIAA1549-BRAF fusion) on tumor growth rates, aiming to identify potential variables to prognosticate further progress or senescence. A total of 53 patients vs 94 patients in the pre- and postoperative cohort, respectively, could be observed over a mean follow-up time of 40.2 vs 60.1 months. Distribution of histopathological diagnosis and tumor sites showed similarity to previously published cohort studies. Comparative analysis of pre- and postoperative TGV showed a significant difference as mean preoperative TGV accounted for 0.264 cm³/mo, while postoperative TGV after 1st, 2nd and 3rd STR showed reduction to 0.085 cm³/mo, 0.024 cm³/mo and -0.016 cm³/mo, respectively (p &amp;lt; 0.001). Results remained significant after excluding patients who had obtained (neo)adjuvant treatment. Resection extent showed remarkable correlation with postoperative reduction of TGV (R = 0.97, P &amp;lt; 0.001). Comparison of postoperative TGV of BRAF V600E mutant LGG and BRAF wild-type LGG showed significant difference of means (0.123 cm³/mo and 0.016 cm³/mo, p = 0.47), consistent to previous analyses, suggesting BRAF V600E positive LGG as a high-risk subgroup. Histological type, tumor location and BRAF-KIAA1549 fusion showed no significant impact on postoperative TGV. The results suggest that surgery, beyond cytoreductive purpose, impacts PLGG kinetics post STR by inducing a significant deceleration of tumor growth. As postoperative growth velocity showed clear correlation to resection extent and residual tumor burden, surgery, as radical as possible while preserving neurological function, appears to remain the mainstay of therapy besides advancing therapeutic approaches.
Predictors of health-related quality of life deterioration in the first year after radical cystectomy with urinary diversion: Results from a single centre randomized controlled trial
Authors: R. Mastroianni, G. Tuderti, U. Anceschi, A.M. Bove, A. Brassetti, M. Ferriero, L. Misuraca, S. Guaglianone, M. Gallucci, G. Simone
Journal: European Urology (2022)
Amplitudes and kinetic of antibodies after second and third doses of BNT162b2 vaccine in nonagenarians and centenarians with and without prior SARS-CoV-2 infection
Authors: Edouard Tuaillon, Amandine Pisoni, Lucie Gamon, Steven Henry, None Anne-Marie Mondain, Patrick Pastor, Philippe Van de Perre, Jean Bousquet, Marie-Christine Picot, Hubert Blain
Journal: Clinical Microbiology and Infection (2022)
Aspects of somatogenic asthenic syndrome in patients with high cardiovascular risk
Authors: A Demikhov, N Demikhova, T Rudenko, A Orlovskiy
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: None. Aim To study frequency and nature of psychopathological symptoms in various forms of somatogenic asthenic syndrome in patients with high cardiovascular risk (CVR). Methods The quantitative anamnestic analysis of medical history, the variational statistics, the probabilistic allocation of clinical signs with estimation of reliability of the results. Among the 199 persons with high CVR and non-psychotic mental disorders: 31 patients had somatogenic asthenic syndrome (SAS), stratified by clinical variants: asthenic (1n2=14); asthenic-anxious (2n2=8); asthenic-subdepressive (3n2=6) and dyssomniac (4n2=3). Results The frequency and kind of pathopsychological symptoms in young people with increased CVR and SAS was studied. Each variant of SAS in patients with high CVR has its features of symptomological structure. More, than in half of cases in asthenic variant of SAS in patients with high CVR, registered a headache, a feeling of heaviness in the head (63.4±12.8%), intolerance to loud sounds and bright lights (57.1±13.2%) and low mood (50.0±13.4%). Patients with high CVR and asthenic-anxious variant of SAS on the first place by the frequency of diagnosing was also weakness (87.5±11.7%), lack of vigor after a night's sleep (87.5±11.7%) and almost with the same frequency were registered fatigue (75.0±15.3%), memory impairment (62.5±17.1%), which in 1.5-3 times exceeded the average in patients with SAS by the frequency; anxiety, absentmindedness were diagnosed in 50.0±17.7% of cases in this subgroup. Prevailing (most common) psychopathological symptoms, significantly more represented than on the average in patients with high CVR and dyssomniac variant of SAS were (at 65-100%): absentmindedness, irritability, fatigue, weakness, anxiety. Most common symptom in patients with high CVR and asthenic variant of SAS was a weakness - in (92.9±6.9)%, and the prevalence was significantly higher, than on the average in group of patients with SAS. There were fatigue (85.7±9.4%), tearfulness (85.7±9.4%), irritability (63.4±12.8%), difficulty falling asleep (57.1±13.2%), the prevalence of which significantly exceeded the average in patients with SAS (p&amp;lt;0.05). In patients with high CVR and asthenic-anxious SAS on the first place by the frequency of diagnosis was also weakness (87.5±11.7%), lack of vigor after a night's sleep (87.5±11.7%) almost on the same frequency was registered fatigue (75.0±15.3%), memory impairment (62.5±17.1%), which in 1.5-3 times exceeded the average in patients with SAS by the frequency. Most common for patients with high CVR and asthenic-subdepressive variant of SAS were: dizziness (83.3±15.2), sleep disorders and restless sleep (66.7±19.2%), touchiness and anguish (66.7±19.2%). Conclusions Ranking of symptoms was made and the major syndromes, depending on the variant of SAS in patients with high CVR, were defined.
Pancreatic Cancer Surveillance in Carriers of a Germline <i>CDKN2A</i> Pathogenic Variant: Yield and Outcomes of a 20-Year Prospective Follow-Up
Authors: Derk C.F. Klatte, Bas Boekestijn, Martin N.J.M. Wasser, Shirin Feshtali Shahbazi, Isaura S. Ibrahim, J. Sven D. Mieog, Saskia A.C. Luelmo, Hans Morreau, Thomas P. Potjer, Akin Inderson, Jurjen J. Boonstra, Friedo W. Dekker, Hans F.A. Vasen, Jeanin E. van Hooft, Bert A. Bonsing, Monique E. van Leerdam
Journal: Journal of Clinical Oncology (2022)

Pancreatic cancer surveillance in high-risk individuals may lead to detection of pancreatic ductal adenocarcinoma (PDAC) at an earlier stage and with improved survival. This study evaluated the yield and outcomes of 20 years of prospective surveillance in a large cohort of individuals with germline pathogenic variants (PVs) in CDKN2A.Prospectively collected data were analyzed from individuals participating in pancreatic cancer surveillance. Surveillance consisted of annual magnetic resonance imaging with magnetic resonance cholangiopancreatography and optional endoscopic ultrasound.Three hundred forty-seven germline PV carriers participated in surveillance and were followed for a median of 5.6 (interquartile range 2.3-9.9) years. A total of 36 cases of PDAC were diagnosed in 31 (8.9%) patients at a median age of 60.4 (interquartile range 51.3-64.1) years. The cumulative incidence of primary PDAC was 20.7% by age 70 years. Five carriers (5 of 31; 16.1%) were diagnosed with a second primary PDAC. Thirty (83.3%) of 36 PDACs were considered resectable at the time of imaging. Twelve cases (12 of 36; 33.3%) presented with stage I disease. The median survival after diagnosis of primary PDAC was 26.8 months, and the 5-year survival rate was 32.4% (95% CI, 19.1 to 54.8). Individuals with primary PDAC who underwent resection (22 of 31; 71.0%) had an overall 5-year survival rate of 44.1% (95% CI, 27.2 to 71.3). Nine (2.6%; 9 of 347) individuals underwent surgery for a suspected malignant lesion, which proved to not be PDAC, and this included five lesions with low-grade dysplasia.This long-term surveillance study demonstrates a high incidence of PDAC in carriers of a PV in CDKN2A. This provides evidence that surveillance in such a high-risk population leads to detection of early-stage PDAC with improved resectability and survival.
MODL-17. The Childhood Brain Cancer Cell Line Atlas: A Resource for Biomarker Identification and Therapeutic Development
Authors: Paul Daniel, Claire Sun, Mateusz Koptyra, Caroline Drinkwater, Nicole Chew, Gabrielle Bradshaw, Melissa Loi, Claire Shi, Motahhareh Tourchi, Sarah Parackal, Wai Chin Chong, Dasun Fernando, Shazia Adjumain, Hoang Nguyen, Dilru Habarakada, Dhanya Sooraj, Duncan Crombie, Nataliya Zhukova, Chris Jones, Jeffrey Rubens, Eric Raabe, Maria Vinci, Matt Dun, Louise Ludlow, Javad Nazarian, Jamie Fletcher, Paul Ekert, David Ziegler, Amos Hong Pheng Loh, Sharon Yin Yee Low, Michelle Monje, Naama Neeman, Bryan Williams, Adam Resnick, Daniel Gough, Jason Cain, Ron Firestein
Journal: Neuro-Oncology (2022)

Abstract Cell lines represent the most versatile and widely used models of cancer and, as such, are critical for identifying and advancing new therapies. Strikingly, there is a significant gap in both the number of childhood brain cancer cell lines and their characterisation compared to their adult counterparts. To address this inequity, we established a childhood brain cancer cell line atlas (publicly available at vicpcc.org.au/dashboard) encompassing over 180 childhood CNS-derived cell lines, representing 20 tumour types and 11 molecular subtypes. Cell lines are characterized by whole genome, RNA-sequencing, phospho- and total proteomics, DNA methylation and ATAC-seq analyses. Multi-omic factor analysis revealed distinct lineage-specified classification of our cell line cohort. In parallel, high throughput drug and CRISPR/Cas9 screens were conducted to map the functional dependencies in over 70 childhood CNS cell lines, including 47 paediatric high grade glioma models. These screens identified both lineage and molecular-subtype specific genetic and drug dependencies, underscoring the utility of this wide-scale approach. Machine based learning approaches to predict genotype-phenotype correlations uncovered distinct paediatric-specific biomarkers of growth dependency, highlighting the unique genetic wiring underlying paediatric CNS tumours. Finally, by integrating functional, molecular and drug profiles of paediatric CNS cell lines, we construct a system to prioritize investigation of novel therapeutic target-biomarkers pairs in specific CNS tumour types.
Racial disparity in breast cancer survivorship: Results of a qualitative research study to identify themes from a series national healthcare provider live virtual forums.
Authors: Jill M. Binkley, Sheryl G. A. Gabram, Lauren E. McCullough, Janae Finley, Dawnovise Fowler, Lisa VanHoose
Journal: Journal of Clinical Oncology (2022)

12091 Background: Significant disparity exists in the diagnosis, treatment, and survivorship outcomes among Black breast cancer (BC) survivors. Unmet physical and emotional needs in BC survivors are well documented, but there is mounting evidence that Black BC survivors have more significant survivorship issues and a greater burden of illness than White counterparts. Barriers to rehabilitation and recovery care exist for all BC survivors; however, they are magnified in Black BC survivors due to systemic racism, healthcare provider bias and discrimination, lack of culturally relevant care models, and socio-economic barriers. There is limited literature on lived personal and professional experiences of racial disparity in BC survivorship. Methods: The purpose of this qualitative research was to document patient, clinician and researchers’ perceptions surrounding contributing factors, lived experiences, and potential solutions to racial disparity in BC survivorship against the contextual background of reported inequities. A narrative approach was utilized to identify themes from a series of four virtual healthcare provider forums that explored lived personal and professional experiences, issues and potential solutions surrounding racial disparity in BC survivorship from October 2020-September 2021. The forums included perspectives of patients, healthcare providers, researchers, and stakeholders in the BC field. The total live and online views for all four forums was 2,093. An independent thematic analysis was performed by the investigators, all of whom have emic perspectives with respect to race and/or breast cancer. Results: Three main themes were independently identified by study investigators: 1. societal and cultural contributing factors contributing to racial disparity in BC survivorship, 2. contribution of healthcare providers and systems to racial disparity in BC survivorship and 3. models of care and research considerations that would reduce racial disparity. These themes were widely echoed by forum participants throughout the series. With respect to solutions, widespread implementation of navigation models and the Prospective Model of Rehabilitation for Women with Breast Cancer that address physical and psychosocial treatment side effects would reduce disparity. The importance of the inclusion of voices of Black BC survivors in community-based participatory research aimed at reducing survivorship disparity is critical. Conclusions: The findings provide compelling documentation of lived personal and professional experiences of racial disparity in BC survivorship. These issues have been described in the literature for nearly two decades. Potential solutions exist and must be enacted immediately to ensure equitable survivorship outcomes for Black individuals following a BC diagnosis.
Comparison of quality of life in patients randomized to high-dose once daily (QD) thoracic radiotherapy (TRT) with standard twice daily (BID) TRT in limited stage small cell lung cancer (LS-SCLC) on CALGB 30610 (Alliance, Sub-study CALGB 70702).
Authors: Apar Kishor Ganti, Amylou C. Dueck, Briant Fruth, Andreas Rimner, Saiama Naheed Waqar, Michael D Mix, William J. Petty, Jeffrey A Bogart
Journal: Journal of Clinical Oncology (2022)

8504 Background: The CALGB 30610 trial demonstrated that 70Gy QD TRT was not associated with a superior overall survival compared to standard BID 45Gy TRT in limited stage small cell lung cancer. Since both arms appeared to provide similar clinical benefit, other factors such as quality of life may help oncologists decide on the best treatment approach for their patients. The present analysis was conducted to compare patients’ quality of life between these regimens in terms of their physical symptoms, physical functioning and psychological state. Methods: In the CALGB 30610 planned sub-study CALGB 70702, patients were administered the FACT-L, FACT Trial Outcome Index-Lung Cancer (FACT-L TOI), FACT-Esophageal Cancer Eating and Swallowing Indices, ECOG Acute Esophagitis Scale, Hospital Anxiety and Depression Scale (HADS), the EQ-5D at baseline and a single item assessing difficulty swallowing at baseline, 3, 5, 7, 12, 26, and 52 weeks after starting radiation therapy. Patients were also asked to assess treatment inconvenience at these time points. The primary endpoints of CALGB 70702 were FACT-L TOI and FACT eating and swallowing subscales at 12 weeks. Mean changes from baseline were compared between arms using general linear mixed models. Results: 417 patients consented to participate in the patient-reported outcomes substudy. The completion rate of the questionnaires was 87% at baseline and 71% at week 52. The FACT-L total score mean worsening was significantly less in the QD arm compared to the BID arm at week 3 (-1.0 vs -7.0; P=.003), and marginally less at week 5 (-5.3 vs -11.0; P=.06). The FACT-L TOI mean worsening was significantly less in the QD arm than in the BID arm at week 3 (-2.9 vs -7.6; P=.003) and greater at week 12 (-7.6 vs -2.8; P=.03). The QD arm also had a lesser EQ-5D index mean worsening at 3 weeks (-0.04 vs 0.03; P=.002). Mean increase in the acute esophagitis score (1.06 vs 2.89; P&lt;.001) and difficulty swallowing (0.39 vs 1.14; P&lt;.001) were significantly greater in the BID arm at week 3. Mean worsening in HADS anxiety was significantly less in the QD arm at week 5 (-1.99 vs -0.95; P=.03). There were no other significant differences at the remaining timepoints between the two arms. Across visits on the QD arm, patients felt that treatment was inconvenient at 26% (96/376) assessments, compared to 33% (116/352) in the BID arm (chi-sq P=.03). Conclusions: Both radiation regimens were well tolerated. However, the QD arm had better quality of life scores at week 3 and was perceived to be less inconvenient. Clinical trial information: NCT00632853.
IMMU-22. Safely targeting GD2 in thalamic diffuse midline glioma with mRNA CAR T cells
Authors: Jessica Foster, Crystal Griffin, Allison Stern, Peter Madsen, Phillip Storm, Adam Resnick
Journal: Neuro-Oncology (2022)

Abstract Chimeric antigen receptor (CAR) T cells targeting the disialoganglioside GD2 have shown promise as a therapeutic for diffuse midline glioma (DMG). However, prior studies raised significant concerns of neurotoxicity and fatality when using virally transduced CAR T cells against midline thalamic tumors. Building upon our prior work optimizing mRNA for use in CAR T cells (Hum Gen Ther, 2019), we hypothesized repeated dosing of transient GD2-directed mRNA CAR T cells could be employed for safe and effective treatment of thalamic DMG. GD2-directed CAR T cells were created using mRNA encoding the 14G2a single chain variable fragment paired with 41BB and CD3-zeta co-stimulatory domains and transfected into human T cells. CAR T cells were tested against the murine thalamic DMG xenograft 7316-6349 via locoregional delivery with an indwelling infusion catheter for repeated dosing. The previously reported fatal neurotoxicity observed in mice using lentiviral CAR T cells could be recapitulated with aggressive dosing. Four doses of 5 x 106 mRNA CAR T cells delivered intratumorally twice a week resulted in median overall survival of 9 days for GD2-treated mice compared to &amp;gt;30 days for CD19-treated controls (p&amp;lt;0.01). This toxicity could be avoided by decreasing the dose and timing of infusions to 2 x 106 mRNA CAR T cells delivered once weekly. Bioluminescent imaging showed regression of tumor in GD2-treated mice compared to CD19-treated controls (radiance fold change -3 x106 versus +20x106 p/sec/cm2/sr, p&amp;lt;0.01). Notably, non-tumor bearing mice treated with GD2-directed CAR T cells quickly developed fatal neurotoxicity within 14 days, suggesting on-target/off-tumor effect of the CAR T cells and a very narrow therapeutic window in the brain. These data highlight the utility of titratable mRNA-based CAR T cell therapy for CNS tumors and establish GD2-directed mRNA CAR T cells as a safe and effective method for treating thalamic DMG.
Genetic Variation in Reproductive Investment Across an Ephemerality Gradient in<i>Daphnia pulex</i>
Authors: Karen B Barnard-Kubow, Dörthe Becker, Connor S Murray, Robert Porter, Grace Gutierrez, Priscilla Erickson, Joaquin C B Nunez, Erin Voss, Kushal Suryamohan, Aakrosh Ratan, Andrew Beckerman, Alan O Bergland
Journal: Molecular Biology and Evolution (2022)

Abstract Species across the tree of life can switch between asexual and sexual reproduction. In facultatively sexual species, the ability to switch between reproductive modes is often environmentally dependent and subject to local adaptation. However, the ecological and evolutionary factors that influence the maintenance and turnover of polymorphism associated with facultative sex remain unclear. We studied the ecological and evolutionary dynamics of reproductive investment in the facultatively sexual model species, Daphnia pulex. We found that patterns of clonal diversity, but not genetic diversity varied among ponds consistent with the predicted relationship between ephemerality and clonal structure. Reconstruction of a multi-year pedigree demonstrated the coexistence of clones that differ in their investment into male production. Mapping of quantitative variation in male production using lab-generated and field-collected individuals identified multiple putative quantitative trait loci (QTL) underlying this trait, and we identified a plausible candidate gene. The evolutionary history of these QTL suggests that they are relatively young, and male limitation in this system is a rapidly evolving trait. Our work highlights the dynamic nature of the genetic structure and composition of facultative sex across space and time and suggests that quantitative genetic variation in reproductive strategy can undergo rapid evolutionary turnover.
A nomogram to predict the prognosis of advanced soft tissue sarcoma patients treated with anlotinib: A real-world population-based study.
Authors: Bin Wang, Jie Liu, Ren shu Zhang, Yu Jiang
Journal: Journal of Clinical Oncology (2022)

e23550 Background: The ALTER0203 randomized controlled trial proved the antitumor activity of anlotinib, a multitargeted tyrosine kinase inhibitor, in 8 subtypes of advanced refractory soft tissue sarcoma (STS). Our previous studies have shown that anlotinib showed antitumor activity in more than 30 STS pathological subtypes in the real world. This study further constructed a nomogram to predict the prognosis of advanced STS patients treated with anlotinib based on real-world data. Methods: We retrospectively analyzed the data of patients with unresectable locally advanced or metastatic STS who received at least one dose of anlotinib from June 2018 to March 2021. A nomogram was developed to predict the survival probability based on the multivariate analysis. The performance of the nomogram was evaluated by concordance index, bootstrap resampling calibration curve and time-dependent ROC curve. Results: A total of 209 patients were included in this study. The median age was 48 years (range 11-85 years), and the median follow-up time was 18.7 months. Based on five independent prognostic factors including ECOG performance status, FNCLCC grade G2-3, poor nutrition, increased neutrophil count, and treatment patterns according to the multivariate analysis, we constructed a nomogram to predict the prognosis of advanced STS patients treated with anlotinib. The concordance index was 0.780. For the prediction of 1-year and 2-year overall survival probability according to the nomogram, the area under the receiver operating characteristic curve was 0.833 and 0.829, respectively. Conclusions: The nomogram based on ECOG performance status, FNCLCC grade, nutritional status, neutrophil count, and treatment patterns can accurately predict the 1-year and 2-year OS probability for advanced STS patients treated with anlotinib.